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NCT Number: NCT03477656

Evaluation of 2 Techniques of Apheresis to Desensitize ABO Incompatible Kidney Transplant Candidates

Kidney transplantation is the treatment of choice for end-stage renal disease. ABO incompatible (ABOi) living donor kidney transplantation is one of the best ways to expand the donors' pool. However, breaking the ABO barrier is possible only with a preconditioning regimen that includes 1) an immunosuppressive strategy using a B-cell depleting agent (rituximab), an induction therapy with polyclonal antibodies, and a maintenance triple immunosuppressive therapy based on calcineurin inhibitors, and 2) a desensitization protocol aiming to decrease the titer of isoagglutinins. For this purpose, several techniques of apheresis are available. To date, two main techniques used in clinical setting are the Double-Filtration PlasmaPheresis (DFPP) and the Antigen-Specific Immunoadsorption (SIA). DFPP permits the depletion of the selective plasma fraction containing Immunoglobulins, while limiting the need for plasma substitution. SIA enables to remove ABO antibodies without a major loss in essential plasma components. To date, no randomized study comparing DFPP and SIA exist. SIA is less often used because of its high cost. However, in order to reduce the number of SIA sessions and consequently its cost, large plasma volume sessions of SIA are performed. ABOi is dramatically more expensive than ABO compatible kidney transplantation. A large part of the difference in the cost is related to the apheresis technique.

Herein, the investigator proposes to describe the efficacy, the safety, and the cost of DFPP and SIA to desensitize ABO incompatible kidney transplant candidates.

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Key information

Conditions

Kidney Transplantation

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University Hospital Toulouse (Hospital Rangueil)

Toulouse, 31059, France

About this study

All recipients will receive an induction therapy with rituximab and polyclonal antibodies, as well as a maintenance therapy by tacrolimus, mycophenolic acid (switched for mTOR (Mechanistic target of rapamycin) inhibitors 1 month after the transplantation to avoid viral infections) and steroids.

The desensitization protocol will be based on the initial titer of isoagglutinin. All patients with an isoagglutinin titer between 1/8 and 1/128 will be included in this monocentric, open label study, and randomized between the DFPP arm (1 to 4 sessions according to the initial titer) and large-plasma SIA (1 to 2 sessions according to the titer). The effectiveness will be evaluated on the ability to obtain the targeted titer before transplantation (1/4) with less than 5 DFPP, or 2 large-plasma volume SIA.

All recipients will be followed for 6 months, and examined for surgical complications, rejection rate, and kidney function. All complications related to desensitization protocol will be reported. Moreover, all cost associated with these two apheresis techniques will be evaluated.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patient eligible for living donor ABO incompatible kidney transplantation
  • Presenting an IsoAgglutinin immunoglobulin G titer (anti-A-B) between 1/8 and 1/128, before desensitization
  • Patient older than 18 years
  • Women of childbearing age must have a pregnancy test before starting the study and undergoing study. They must take an effective and acceptable method of contraception before starting the study and throughout the study period. Sexually active men should use a condom throughout the course of the study
  • Patient able to sign an informed consent form
  • Patient affiliated with a social security scheme

Exclusion criteria

  • Presence of anti-HLA (Human Leucocyte Antigens) allo-antibodies
  • Patient with comorbidities that prevent desensitization protocols
  • Women who are pregnant, or who may become pregnant or breastfeeding women
  • History of hypersensitivity related to a component of the apheresis membrane
  • Subjects under legal protection
  • Subjects participating in another interventional research protocol or in an exclusion period from another interventional research protocol

Treatment and study plan

Large volume specific immunoadsorption

Procedure

1 to 2 sessions of large volume specific immunoadsorption using GLYCOSORB®-ABO column

Double Filtration Plasmapheresis

Procedure

1 to 5 sessions of double filtration plasmapheresis

Primary outcomes

  1. Success rate

    Time frame: the day of transplantation

    % of subjects with the targeted isoagglutinin titer (≤1/4) before transplantation with less than 5 DFPP sessions (for the DFPP arm) or 2 large plasma volume specific immunoadsorption sessions (for the specific immunoadsorption arm)

Secondary outcomes

  1. Differential cost-efficacy ratio of support for patients receiving a live donor kidney transplant Incompatible ABO and benefiting from a desensitization procedure

    Time frame: 7 months

    Direct medical costs ( treatments costs, costs of hospital stays, costs of outpatient cares) will be evaluated from the society point of view.

    A cost-efficacy analysis, comparative of medical consequences, measured in terms of number of complications related to the technique and post surgical at 7 months, and the economic consequences will be realized.

  2. Surgical complication rate during the desensitization sessions

    Time frame: From the first desensitization session to the last one, assessed up to 10 days

    % of subjects with surgical complications during the desensitization sessions

  3. Surgical complication rate during the transplantation surgery

    Time frame: During the transplantation surgery

    % of subjects with surgical complications during the transplantation surgery

  4. Thrombotic complication rate during the desensitization sessions

    Time frame: From the first desensitization session to the last one, assessed up to 10 days

    % of subjects with thrombotic complications during the desensitization sessions

  5. Thrombotic complication rate 1 week after transplantation surgery

    Time frame: 1 week after transplantation surgery

    % of subjects with thrombotic complications until 1 week after transplantation surgery

  6. Rate of bleeding and/or hematoma on vascular access during the desensitization sessions

    Time frame: From the first desensitization session to the last one, assessed up to 10 days

    % of subjects with bleeding and/or hematoma on vascular access during the desensitization sessions

  7. Rate of hematoma occurrence during the transplantation surgery

    Time frame: During the transplantation surgery

    % of subjects with hematoma during the transplantation surgery

  8. Rate of occurrences of hemorrhage away from vascular access during the desensitization sessions

    Time frame: From the first desensitization session to the last one, assessed up to 10 days

    % of subjects with hemorrhage away from vascular access during the desensitization sessions

  9. Rate of occurrences of allergy to the components of the membrane or of the blood circuit (tube set) during the desensitization sessions

    Time frame: From the first desensitization session to the last one, assessed up to 10 days

    % of subjects with allergy to the components of the membrane or of the blood circuit (tube set) during the desensitization sessions

  10. Rate of occurrences of allergy to the components of the membrane or of the blood circuit (tube set) 1 week after transplantation surgery

    Time frame: 1 week after transplantation surgery

    % of subjects with allergy to the components of the membrane or of the blood circuit (tube set) until 1 week after transplantation surgery

  11. Blood transfusion rate before transplantation

    Time frame: Before transplantation

    % of subjects who received blood transfusion before transplantation

  12. Blood transfusion rate during the transplantation surgery

    Time frame: During the transplantation surgery

    % of subjects who received blood transfusion during the transplantation surgery

  13. Blood transfusion rate 1 week after transplantation surgery

    Time frame: 1 week after transplantation surgery

    % of subjects who received blood transfusion until 1 week after transplantation surgery

  14. Occurrence rate of deep vein or graft vein thrombosis during the transplantation surgery

    Time frame: During the transplantation surgery

    % of subjects with deep vein or graft vein thrombosis during the transplantation surgery

  15. Graft ablation rate 1 week after transplantation surgery

    Time frame: 1 week after transplantation surgery

    % of subjects with graft ablation until 1 week after transplantation surgery

  16. Complication rate on surgical area 1 week after transplantation surgery

    Time frame: 1 week after transplantation surgery

    % of subjects with complication on the surgical area until 1 week after transplantation surgery

  17. Infectious complication rate 1 week after transplantation surgery

    Time frame: 1 week after transplantation surgery

    % of subjects with Infectious complication until 1 week after transplantation surgery

  18. Need for dialysis session(s) 1 week after transplantation surgery

    Time frame: 1 week after transplantation surgery

    number of subjects for which one or several dialysis session(s) is necessary until 1 week after transplantation surgery

  19. Graft rejection rate 1 month after transplantation surgery

    Time frame: 1 month after transplantation surgery

    % of subjects with graft rejection until 1 month after transplantation surgery

  20. Graft rejection rate 3 months after transplantation surgery

    Time frame: 3 months after transplantation surgery

    % of subjects with graft rejection until 3 months after transplantation surgery

  21. Graft rejection rate 6 months after transplantation surgery

    Time frame: 6 months after transplantation surgery

    % of subjects with graft rejection until 6 months after transplantation surgery

  22. Renal function 1 month after transplantation surgery

    Time frame: 1 month after transplantation surgery

    creatinine 1 month after transplantation surgery

  23. Renal function 3 months after transplantation surgery

    Time frame: 3 months after transplantation surgery

    creatinine 3 months after transplantation surgery

  24. Renal function 6 months after transplantation surgery

    Time frame: 6 months after transplantation surgery

    creatinine 6 months after transplantation surgery

  25. Change in hemostasis parameters from before the desensitization protocol to after

    Time frame: the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)

    plasma level of fibrinogen clotting factors

  26. Change in hemostasis parameters from before the desensitization protocol to after

    Time frame: the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)

    plasma level of factor XIII

  27. Change in hemostasis parameters from before the desensitization protocol to after

    Time frame: the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)

    plasma level of thrombin-antithrombin complex

  28. Change in hemostasis parameters from before the desensitization protocol to after

    Time frame: the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)

    plasma level of platelet secretion proteins (sCD40L, PF4)

  29. Change in hemostasis parameters from before the desensitization protocol to after

    Time frame: the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)

    plasma level of ADAMTS13 metalloprotease

  30. Change in hemostasis parameters from before the desensitization protocol to after

    Time frame: the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)

    Von Willebrand factor (cleaved form)

  31. Change in hemostasis parameters from before the desensitization protocol to after

    Time frame: the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)

    blood level of platelet-monocyte complexes

  32. Change in hemostasis parameters from before the desensitization protocol to after

    Time frame: the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)

    blood level of platelet-neutrophil polynuclear complexes

  33. Change in hemostasis parameters from before the desensitization protocol to after

    Time frame: the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)

    endogenous thrombin potential

  34. Change in hemostasis parameters from before the desensitization protocol to after

    Time frame: the day of the first desensitization session (just before the session) and the day after the last desensitization session (up to 11 days)

    peak thrombin

Sponsors and collaborators

Lead sponsor

University Hospital, Toulouse

Other

Registry information

Official study title

Evaluation of 2 Techniques of Apheresis to Desensitize ABO Incompatible Kidney Transplant Candidates: Double Filtration PlasmaPheresis (DFPP) vs Large Plasma Volume Specific ImmunoAdsorption

Acronym: DADI

Important dates

Study start
2018
Primary completion
2023
Study completion
2023
First posted
Mar 26, 2018
Registry last updated
Apr 12, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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